2-phenylindole-linked nitroimidazoles as potential radiosensitizers for estrogen receptor positive tumors.
5-Hydroxy-2-(4-hydroxyphenyl)-3-methylindole was linked to nitroimidazoles by tetramethylene and hexamethylene spacer groups. Derivatives with a C6-spacer (4c and 4d) exhibited high binding affinities for the estrogen receptor (RBA = 3.5; estradiol: 100), a prerequisite for a selective uptake by estrogen receptor positive tumors. Both compounds inhibited the growth of hormone-sensitive human MCF-7 mammary tumor cells at concentrations greater than 5 x 10(-6) M, presumably due to the weak antiestrogenic effect observed in the mouse uterine weight test.
Erber
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S
Institut für Pharmazie, Universität Regensburg.
von Angerer
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D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014599:Uterus / Q000187:drug effects
D007211:Indoles; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D011960:Receptors, Estrogen